Trial Outcomes & Findings for A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause - 2 (NCT NCT04003142)

NCT ID: NCT04003142

Last Updated: 2024-11-05

Results Overview

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 501 participants
• Primary outcome timeframe: Baseline and week 4
• Results posted on: 2024-11-05

Participant Flow

Postmenopausal women participants 40 to 65 years of age who had moderate to severe vasomotor symptoms (VMS) and seeking treatment or relief for VMS associated with menopause, confirmed as menopausal, had to have 7 to 8 moderate to severe VMS per day within the 10 days prior to randomization and who met the inclusion criteria and none of the exclusion criteria were enrolled in this study.

Prior to randomization, participants had a screening period during which a minimum 10-day collection of baseline VMS frequency and severity assessments were performed.

Participant milestones

Measure	Double-blind Period: Placebo Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Double-blind Period (12 Weeks) STARTED	168	166	167	0	0
Double-blind Period (12 Weeks) Treated	167	166	167	0	0
Double-blind Period (12 Weeks) COMPLETED	151	152	155	0	0
Double-blind Period (12 Weeks) NOT COMPLETED	17	14	12	0	0
Extension Period (40 Weeks) STARTED	0	152	154	76	75
Extension Period (40 Weeks) COMPLETED	0	125	132	63	63
Extension Period (40 Weeks) NOT COMPLETED	0	27	22	13	12

Reasons for withdrawal

Measure	Double-blind Period: Placebo Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Double-blind Period (12 Weeks) Adverse Event	1	1	2	0	0
Double-blind Period (12 Weeks) Lost to Follow-up	2	1	2	0	0
Double-blind Period (12 Weeks) Protocol Deviation	1	5	0	0	0
Double-blind Period (12 Weeks) Withdrawal by Subject	11	6	6	0	0
Double-blind Period (12 Weeks) Miscellaneous	2	1	2	0	0
Extension Period (40 Weeks) Adverse Event	0	4	4	2	3
Extension Period (40 Weeks) Death	0	0	0	0	1
Extension Period (40 Weeks) Lost to Follow-up	0	2	1	2	1
Extension Period (40 Weeks) Protocol Deviation	0	0	2	0	0
Extension Period (40 Weeks) Withdrawal by Subject	0	17	14	9	5
Extension Period (40 Weeks) Miscellaneous	0	4	1	0	2

Baseline Characteristics

Full analysis set (FAS) consisted of all randomized participants who took at least 1 dose of study intervention.

Baseline characteristics by cohort

Measure	Double-blind Period: Placebo n=168 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg n=166 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg n=167 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD from week 13 up to Week 52 during extension treatment period.	Total n=501 Participants Total of all reporting groups
Age, Continuous	54.6 Years STANDARD_DEVIATION 4.6 • n=168 Participants	53.9 Years STANDARD_DEVIATION 4.9 • n=166 Participants	54.3 Years STANDARD_DEVIATION 5.4 • n=167 Participants	54.3 Years STANDARD_DEVIATION 5 • n=501 Participants
Sex: Female, Male Female	168 Participants n=168 Participants	166 Participants n=166 Participants	167 Participants n=167 Participants	501 Participants n=501 Participants
Sex: Female, Male Male	0 Participants n=168 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants	0 Participants n=501 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=168 Participants	34 Participants n=166 Participants	41 Participants n=167 Participants	108 Participants n=501 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants n=168 Participants	132 Participants n=166 Participants	126 Participants n=167 Participants	392 Participants n=501 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=168 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants	1 Participants n=501 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=168 Participants	0 Participants n=166 Participants	1 Participants n=167 Participants	1 Participants n=501 Participants
Race (NIH/OMB) Asian	1 Participants n=168 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants	1 Participants n=501 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=168 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants	0 Participants n=501 Participants
Race (NIH/OMB) Black or African American	31 Participants n=168 Participants	35 Participants n=166 Participants	33 Participants n=167 Participants	99 Participants n=501 Participants
Race (NIH/OMB) White	135 Participants n=168 Participants	131 Participants n=166 Participants	132 Participants n=167 Participants	398 Participants n=501 Participants
Race (NIH/OMB) More than one race	1 Participants n=168 Participants	0 Participants n=166 Participants	1 Participants n=167 Participants	2 Participants n=501 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=168 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants	0 Participants n=501 Participants
Frequency of Moderate and Severe VMS per 24 hours	11.59 VMS per day STANDARD_DEVIATION 5.02 • n=167 Participants • Full analysis set (FAS) consisted of all randomized participants who took at least 1 dose of study intervention.	11.23 VMS per day STANDARD_DEVIATION 4.88 • n=166 Participants • Full analysis set (FAS) consisted of all randomized participants who took at least 1 dose of study intervention.	11.79 VMS per day STANDARD_DEVIATION 8.26 • n=167 Participants • Full analysis set (FAS) consisted of all randomized participants who took at least 1 dose of study intervention.	11.54 VMS per day STANDARD_DEVIATION 6.25 • n=500 Participants • Full analysis set (FAS) consisted of all randomized participants who took at least 1 dose of study intervention.
Severity of Moderate and Severe VMS per 24 hours	2.41 Score on a scale STANDARD_DEVIATION 0.32 • n=167 Participants • FAS population	2.44 Score on a scale STANDARD_DEVIATION 0.33 • n=166 Participants • FAS population	2.41 Score on a scale STANDARD_DEVIATION 0.34 • n=167 Participants • FAS population	2.42 Score on a scale STANDARD_DEVIATION 0.33 • n=500 Participants • FAS population

PRIMARY outcome

Timeframe: Baseline and week 4

Population: Full analysis set (FAS) (consisted of all randomized participants who took at least 1 dose of study intervention) with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.

Outcome measures

Measure	Double-blind Period: Placebo n=151 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=155 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=155 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 4	-3.72 VMS per day Standard Error 0.33	-5.53 VMS per day Standard Error 0.33	-6.26 VMS per day Standard Error 0.33	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

Population: FAS population with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.

Outcome measures

Measure	Double-blind Period: Placebo n=140 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=133 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=145 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Frequency of Moderate to Severe VMS at Week 12	-4.97 VMS per day Standard Error 0.39	-6.83 VMS per day Standard Error 0.39	-7.50 VMS per day Standard Error 0.39	—	—

PRIMARY outcome

Timeframe: Baseline and week 4

Population: FAS population with available data at specified time point.

Severity of moderate to severe VMS per day at post baseline visit was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).

Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.

Outcome measures

Measure	Double-blind Period: Placebo n=151 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=155 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=155 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 4	-0.32 Score on a scale Standard Error 0.05	-0.47 Score on a scale Standard Error 0.05	-0.61 Score on a scale Standard Error 0.05	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

Population: FAS population with available data at specified time point.

Severity of moderate to severe VMS per day at post baseline visit was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).

Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.

Outcome measures

Measure	Double-blind Period: Placebo n=140 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=133 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=145 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Severity of Moderate to Severe VMS at Week 12	-0.48 Score on a scale Standard Error 0.06	-0.64 Score on a scale Standard Error 0.06	-0.77 Score on a scale Standard Error 0.06	—	—

SECONDARY outcome

Timeframe: Baseline and week 12

Population: FAS population with available data at specified time point.

The PROMIS SD SF 8b assesses self-reported sleep disturbance over the past 7 days and includes perceptions of restless sleep; satisfaction with sleep; refreshing sleep; difficulties sleeping, getting to sleep or staying asleep; amount of sleep; and sleep quality. Because it assesses the participants experience of sleep disturbance, the measure does not focus on specific sleep-disorder symptoms or ask participants to report objective measures of sleep (e.g., total amount of sleep, time to fall asleep and amount of wakefulness during sleep). Responses to each of the 8 items range from 1 (no disturbed sleep) to 5 (disturbed sleep), and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS SD SF 8b indicate more of the disturbed sleep.

Outcome measures

Measure	Double-blind Period: Placebo n=143 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=139 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=145 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Patient-reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b) Total Score at Week 12	-3.4 Score on a scale Standard Error 0.5	-4.1 Score on a scale Standard Error 0.5	-5.5 Score on a scale Standard Error 0.5	—	—

SECONDARY outcome

Timeframe: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10, and 11

Population: FAS population with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.

Outcome measures

Measure	Double-blind Period: Placebo n=166 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=164 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=158 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 3	-3.56 VMS per day Standard Error 0.32	-5.29 VMS per day Standard Error 0.32	-5.95 VMS per day Standard Error 0.32	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 1	-2.32 VMS per day Standard Error 0.28	-3.62 VMS per day Standard Error 0.29	-4.03 VMS per day Standard Error 0.29	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 2	-3.06 VMS per day Standard Error 0.32	-4.82 VMS per day Standard Error 0.32	-5.03 VMS per day Standard Error 0.32	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 5	-4.05 VMS per day Standard Error 0.34	-5.89 VMS per day Standard Error 0.34	-6.71 VMS per day Standard Error 0.34	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 6	-4.25 VMS per day Standard Error 0.33	-6.03 VMS per day Standard Error 0.33	-6.91 VMS per day Standard Error 0.33	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 7	-4.44 VMS per day Standard Error 0.35	-6.24 VMS per day Standard Error 0.35	-6.78 VMS per day Standard Error 0.35	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 8	-4.48 VMS per day Standard Error 0.37	-6.25 VMS per day Standard Error 0.37	-6.86 VMS per day Standard Error 0.37	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 9	-4.88 VMS per day Standard Error 0.38	-6.54 VMS per day Standard Error 0.38	-7.39 VMS per day Standard Error 0.38	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 10	-4.83 VMS per day Standard Error 0.38	-6.74 VMS per day Standard Error 0.38	-7.47 VMS per day Standard Error 0.38	—	—
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 11	-4.90 VMS per day Standard Error 0.38	-6.76 VMS per day Standard Error 0.38	-7.46 VMS per day Standard Error 0.37	—	—

SECONDARY outcome

Timeframe: Baseline and weeks 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11

Population: FAS population with available data at specified time point.

Severity of moderate to severe VMS per day at post baseline visit was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).

Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.

Outcome measures

Measure	Double-blind Period: Placebo n=166 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=164 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=158 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 2	-0.24 Score on a scale Standard Error 0.04	-0.41 Score on a scale Standard Error 0.04	-0.42 Score on a scale Standard Error 0.04	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 3	-0.31 Score on a scale Standard Error 0.04	-0.42 Score on a scale Standard Error 0.04	-0.54 Score on a scale Standard Error 0.04	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 7	-0.42 Score on a scale Standard Error 0.05	-0.58 Score on a scale Standard Error 0.05	-0.70 Score on a scale Standard Error 0.05	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 1	-0.18 Score on a scale Standard Error 0.03	-0.32 Score on a scale Standard Error 0.03	-0.34 Score on a scale Standard Error 0.03	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 5	-0.37 Score on a scale Standard Error 0.05	-0.53 Score on a scale Standard Error 0.05	-0.66 Score on a scale Standard Error 0.05	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 6	-0.37 Score on a scale Standard Error 0.05	-0.55 Score on a scale Standard Error 0.05	-0.65 Score on a scale Standard Error 0.05	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 8	-0.43 Score on a scale Standard Error 0.05	-0.56 Score on a scale Standard Error 0.05	-0.69 Score on a scale Standard Error 0.05	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 9	-0.46 Score on a scale Standard Error 0.06	-0.59 Score on a scale Standard Error 0.06	-0.74 Score on a scale Standard Error 0.06	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 10	-0.45 Score on a scale Standard Error 0.06	-0.64 Score on a scale Standard Error 0.06	-0.76 Score on a scale Standard Error 0.06	—	—
Change From Baseline in The Mean Severity of Moderate, and Severe VMS to Each Study Week Up to Week 12 Week 11	-0.46 Score on a scale Standard Error 0.06	-0.67 Score on a scale Standard Error 0.06	-0.77 Score on a scale Standard Error 0.06	—	—

SECONDARY outcome

Timeframe: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Population: FAS population with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.

Outcome measures

Measure	Double-blind Period: Placebo n=166 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=164 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=158 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 1	-20.82 Percent change Standard Error 2.42	-32.98 Percent change Standard Error 2.43	-36.50 Percent change Standard Error 2.45	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 2	-29.21 Percent change Standard Error 2.69	-43.82 Percent change Standard Error 2.69	-45.16 Percent change Standard Error 2.71	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 4	-34.72 Percent change Standard Error 2.78	-51.06 Percent change Standard Error 2.77	-56.37 Percent change Standard Error 2.77	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 6	-39.64 Percent change Standard Error 2.73	-54.42 Percent change Standard Error 2.73	-62.30 Percent change Standard Error 2.73	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 8	-41.84 Percent change Standard Error 2.86	-56.22 Percent change Standard Error 2.86	-62.42 Percent change Standard Error 2.84	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 3	-33.17 Percent change Standard Error 2.76	-48.68 Percent change Standard Error 2.75	-53.42 Percent change Standard Error 2.76	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 5	-37.88 Percent change Standard Error 2.75	-53.50 Percent change Standard Error 2.75	-60.76 Percent change Standard Error 2.74	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 7	-40.91 Percent change Standard Error 2.84	-55.88 Percent change Standard Error 2.84	-62.38 Percent change Standard Error 2.83	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 9	-45.87 Percent change Standard Error 2.88	-58.01 Percent change Standard Error 2.88	-65.60 Percent change Standard Error 2.86	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 10	-45.58 Percent change Standard Error 2.83	-59.98 Percent change Standard Error 2.82	-65.68 Percent change Standard Error 2.81	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 11	-45.41 Percent change Standard Error 2.88	-60.37 Percent change Standard Error 2.87	-65.56 Percent change Standard Error 2.86	—	—
Mean Percent Change in The Frequency of Moderate And Severe Vasomotor Symptoms From Baseline to Each Study Week Up to Week 12 Week 12	-46.91 Percent change Standard Error 2.87	-60.55 Percent change Standard Error 2.87	-65.85 Percent change Standard Error 2.85	—	—

SECONDARY outcome

Timeframe: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Population: FAS population with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Participant has >=50% reduction from baseline to each post baseline week for the frequency of moderate to severe VMS.

Outcome measures

Measure	Double-blind Period: Placebo n=167 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=166 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=167 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 1	28 Participants	46 Participants	58 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 2	39 Participants	71 Participants	71 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 3	48 Participants	81 Participants	89 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 4	44 Participants	84 Participants	88 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 5	54 Participants	84 Participants	98 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 6	53 Participants	81 Participants	95 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 7	55 Participants	84 Participants	92 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 9	64 Participants	84 Participants	98 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 8	56 Participants	81 Participants	103 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 10	62 Participants	85 Participants	103 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 11	60 Participants	94 Participants	105 Participants	—	—
Number of Participants With Percent Reduction of >=50% in the Mean Frequency of Moderate and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 12	71 Participants	84 Participants	101 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Population: FAS population with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization. Participant has 100% reduction from baseline to each post baseline week for the frequency of moderate to severe VMS.

Outcome measures

Measure	Double-blind Period: Placebo n=167 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=166 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=167 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 8	10 Participants	17 Participants	22 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 1	1 Participants	1 Participants	3 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 2	3 Participants	8 Participants	4 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 3	5 Participants	4 Participants	11 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 4	3 Participants	10 Participants	17 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 5	3 Participants	12 Participants	11 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 6	9 Participants	12 Participants	17 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 7	9 Participants	13 Participants	18 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 9	9 Participants	14 Participants	18 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 10	11 Participants	17 Participants	25 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 11	9 Participants	15 Participants	28 Participants	—	—
Number of Participants With Mean Percent Reduction of 100% in The Mean Frequency of Moderate, and Severe VMS From Baseline to Each Study Week Up to Week 12 Week 12	9 Participants	15 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)

Population: FAS population with available data at specified time point.

The frequency of moderate to severe VMS was the number of moderate to severe VMS per 24 hours. A daily frequency per week was derived by taking the mean of the data over 7 days. Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed). Baseline was the average number of moderate to severe VMS per 24 hours based on the non-missing values in the 10 days immediately prior to randomization.

Outcome measures

Measure	Double-blind Period: Placebo n=131 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=134 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=62 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=60 Participants Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Frequency of Moderate, and Severe VMS at Week 24	-7.86 VMS per day Standard Deviation 4.21	-7.96 VMS per day Standard Deviation 4.53	-9.01 VMS per day Standard Deviation 5.80	-7.08 VMS per day Standard Deviation 5.40	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks of fezolinetant exposure (week 36 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)

Population: FAS population with available data at specified time point.

Severity of moderate to severe VMS per day at post baseline visit was calculated as follows:

[(number of mild hot flashes per day x 1) + (number of moderate hot flashes per day x 2) + (number of severe hot flashes per day x 3)]/Total number of daily mild/moderate/severe hot flashes Moderate VMS was defined as sensation of heat with sweating/dampness, but was able to continue activity. If at night, participant woke up because she was feeling hot and/or was sweating, but no action was necessary other than rearranging the bed sheets. Severe VMS was defined as sensation of intense heat with sweating, caused disruption of activity. If at night, participant woke up hot and was sweating and needed to take action (e.g., remove layers of clothes, open the window, or get out of bed).

Severity was zero for participants that had no mild or moderate or severe VMS. Higher scores indicates greater severity.

Outcome measures

Measure	Double-blind Period: Placebo n=131 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=134 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=62 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=60 Participants Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Change From Baseline in The Mean Severity of Moderate, and Severe VMS at Week 24	-0.85 Score on a scale Standard Deviation 0.88	-0.90 Score on a scale Standard Deviation 0.80	-0.78 Score on a scale Standard Deviation 0.85	-0.95 Score on a scale Standard Deviation 0.88	—

SECONDARY outcome

Timeframe: Weeks 4, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52 of fezolinetant exposure (weeks 16, 24, 28, 32, 36, 40, 44, 48 and 52 for arms Placebo/Fezolinetant 30 mg and Placebo/Fezolinetant 45 mg)

Population: FAS population with available data at specified time point.

The PGI is comprised of 2 companion 1-item PRO measures analogous to the Clinical Global Impression (CGI) scales. These measures provide brief, stand-alone global assessments prior to and after initiating a study medication. Patient-perceived change from the initiation of treatment (PGI-C)-VMS is used to evaluate meaningful within-person changes over time in VMS. This measure provides patient-perceived change from the initiation of treatment.

The PGI-C VMS asks: "Compared to the beginning of this study, how would you rate your HFs/night sweats now?" Subject ratings range from (1) much better to (7) much worse. Participant ratings range from 1=much better, 2= moderately better, 3= a little better, 4= no change, 5= a little worse, 6= moderately worse, 7= much worse.

Outcome measures

Measure	Double-blind Period: Placebo n=151 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=155 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=159 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=67 Participants Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=69 Participants Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4:Much worse	2 Participants	0 Participants	1 Participants	—	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: A little better	36 Participants	29 Participants	32 Participants	11 Participants	10 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: No change	39 Participants	19 Participants	8 Participants	4 Participants	4 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: A little worse	6 Participants	1 Participants	1 Participants	1 Participants	4 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: Moderately worse	2 Participants	2 Participants	0 Participants	0 Participants	1 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: Moderately better	—	0 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: A little better	—	0 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: No change	—	0 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: A little worse	—	0 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: Moderately worse	—	0 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: Much worse	—	1 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: Much better	—	1 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: Moderately better	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: A little better	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: No change	—	1 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: A little worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: Moderately worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: Much better	—	68 Participants	76 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: Moderately better	—	31 Participants	33 Participants	1 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: A little better	—	22 Participants	22 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: No change	—	9 Participants	4 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: A little worse	—	1 Participants	3 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: Moderately worse	—	2 Participants	1 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 24: Much worse	—	1 Participants	0 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: Much better	—	1 Participants	0 Participants	1 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: Moderately better	—	0 Participants	0 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: A little better	—	0 Participants	0 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: No change	—	0 Participants	0 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: A little worse	—	0 Participants	0 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: Moderately worse	—	0 Participants	0 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 28: Much worse	—	0 Participants	1 Participants	0 Participants	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: Much better	—	—	1 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: Moderately better	—	—	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: A little better	—	—	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: No change	—	—	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: Moderately worse	—	—	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: Much worse	—	—	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: A little better	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: No change	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: A little worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: Moderately worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: Much better	—	—	—	33 Participants	31 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: Moderately better	—	—	—	14 Participants	13 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: A little better	—	—	—	5 Participants	8 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: No change	—	—	—	3 Participants	2 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: A little worse	—	—	—	0 Participants	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: Moderately worse	—	—	—	0 Participants	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 40: Much worse	—	—	—	0 Participants	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: Much better	—	2 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: Moderately better	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: A little better	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: No change	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: A little worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: Moderately worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 44: Much worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: Much better	—	60 Participants	77 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: Moderately better	—	25 Participants	22 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: A little better	—	14 Participants	13 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: No change	—	4 Participants	2 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: A little worse	—	1 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: Moderately worse	—	1 Participants	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 52: Much worse	—	2 Participants	2 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4: Much better	25 Participants	61 Participants	68 Participants	—	2 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4:Moderately better	23 Participants	21 Participants	32 Participants	—	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4:A little better	46 Participants	42 Participants	42 Participants	—	1 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4:No change	43 Participants	29 Participants	16 Participants	—	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4:A little worse	6 Participants	2 Participants	0 Participants	—	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 4:Moderately worse	6 Participants	0 Participants	0 Participants	—	0 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: Much better	35 Participants	68 Participants	71 Participants	40 Participants	30 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: Moderately better	24 Participants	25 Participants	37 Participants	11 Participants	18 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 12: Much worse	2 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 16: Much better	—	0 Participants	2 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 20: Much worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: Much worse	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 32: A little worse	—	—	0 Participants	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: Much better	—	0 Participants	—	—	—
Number of Participants in Each Category of Patient's Global Impression of Change (PGIC) in VMS at Each Visit Week 36: Moderately better	—	1 Participants	—	—	—

SECONDARY outcome

Timeframe: From first dose date up to 21 days after last dose (up to 55 weeks)

Population: Safety analysis set consisted of all randomized participants who took at least 1 dose of study intervention.

An AE is any untoward medical occurrence in a participant administered a study drug, & which does not necessarily have to have a causal relationship with treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with use of a medicinal product (mp) whether or not considered related to the mp. An AE is considered "serious" if it results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, Results in congenital anomaly or birth defect, requires inpatient hospitalization or leads to prolongation of hospitalization, hospitalization for treatment/observation/examination caused by AE is to be considered as serious, discontinuation due to increases in liver enzymes, other medically important events. TEAE was defined as an AE observed from first dose date up to 21 days after last dose.

Outcome measures

Measure	Double-blind Period: Placebo n=167 Participants Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg n=166 Participants Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment.	Double-blind Period: Fezolinetant 45 mg n=167 Participants Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=76 Participants Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=75 Participants Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Number of Participants With Adverse Events Treatment Emergent Adverse Events (TEAE)	54 Participants	107 Participants	106 Participants	43 Participants	45 Participants
Number of Participants With Adverse Events Drug-related TEAE	11 Participants	33 Participants	30 Participants	8 Participants	8 Participants
Number of Participants With Adverse Events Serious TEAE	0 Participants	9 Participants	8 Participants	2 Participants	4 Participants
Number of Participants With Adverse Events Drug-related serious TEAE	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events TEAE leading to death	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events Drug-related TEAE leading to death	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events TEAE leading to withdrawal of treatment	1 Participants	4 Participants	7 Participants	2 Participants	3 Participants
Number of Participants With Adverse Events Drug-related TEAE leading to withdrawal of treatment	0 Participants	1 Participants	6 Participants	1 Participants	2 Participants
Number of Participants With Adverse Events Death	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

Adverse Events

Double-blind Period: Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg

Serious events: 9 serious events

Other events: 20 other events

Deaths: 0 deaths

Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg

Serious events: 8 serious events

Other events: 34 other events

Deaths: 0 deaths

Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg

Serious events: 4 serious events

Other events: 12 other events

Deaths: 1 deaths

Serious adverse events

Measure	Double-blind Period: Placebo n=167 participants at risk Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg n=166 participants at risk Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg n=167 participants at risk Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg n=76 participants at risk Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=75 participants at risk Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Cardiac disorders Atrial fibrillation	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/76 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Cardiac disorders Coronary artery disease	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
General disorders Chest pain	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
General disorders Non-cardiac chest pain	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Hepatobiliary disorders Biliary dyskinesia	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Hepatobiliary disorders Cholecystitis acute	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Hepatobiliary disorders Hepatotoxicity	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/75 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)
Infections and infestations COVID-19	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.2% 2/166 • Number of events 2 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Infections and infestations Tooth infection	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Injury, poisoning and procedural complications Foot fracture	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/75 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)
Injury, poisoning and procedural complications Limb injury	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Injury, poisoning and procedural complications Limb traumatic amputation	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Injury, poisoning and procedural complications Multiple injuries	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/75 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)
Injury, poisoning and procedural complications Posterior tibial nerve injury	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Injury, poisoning and procedural complications Skin laceration	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/76 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/75 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/166 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/166 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/76 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)

Other adverse events

Measure	Double-blind Period: Placebo n=167 participants at risk Participants received fezolinetant matching placebo (two fezolinetant matching placebo tablets) orally, once daily (QD) up to week 12 during double-blind treatment period.	Double-blind Period: Fezolinetant 30 mg/Extension Period: Fezolinetant 30 mg n=166 participants at risk Participants received fezolinetant 30 mg (one 30 mg fezolinetant tablet and one placebo tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 30 mg orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Fezolinetant 45 mg/Extension Period: Fezolinetant 45 mg n=167 participants at risk Participants received fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD up to week 12 during double-blind treatment period followed by fezolinetant 45 mg (one 30 mg tablet and one 15 mg tablet) orally, QD from week 13 up to Week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 30 mg n=76 participants at risk Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 30 mg orally, QD from week 13 up to week 52 during extension treatment period.	Double-blind Period: Placebo/Extension Period: Fezolinetant 45 mg n=75 participants at risk Participants who received placebo during double-blind treatment period were re-randomized to receive fezolinetant 45 mg orally, QD from week 13 up to week 52 during extension treatment period.
Infections and infestations COVID-19	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	4.8% 8/166 • Number of events 8 • From first dose date up to 21 days after last dose (up to 55 weeks)	9.0% 15/167 • Number of events 15 • From first dose date up to 21 days after last dose (up to 55 weeks)	5.3% 4/76 • Number of events 4 • From first dose date up to 21 days after last dose (up to 55 weeks)	4.0% 3/75 • Number of events 3 • From first dose date up to 21 days after last dose (up to 55 weeks)
Investigations Blood creatine phosphokinase increased	0.00% 0/167 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.2% 2/166 • Number of events 2 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.8% 3/167 • Number of events 3 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/76 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	6.7% 5/75 • Number of events 6 • From first dose date up to 21 days after last dose (up to 55 weeks)
Nervous system disorders Headache	2.4% 4/167 • Number of events 4 • From first dose date up to 21 days after last dose (up to 55 weeks)	4.8% 8/166 • Number of events 9 • From first dose date up to 21 days after last dose (up to 55 weeks)	7.2% 12/167 • Number of events 14 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.3% 1/76 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	5.3% 4/75 • Number of events 5 • From first dose date up to 21 days after last dose (up to 55 weeks)
Vascular disorders Hot flush	0.60% 1/167 • Number of events 1 • From first dose date up to 21 days after last dose (up to 55 weeks)	1.8% 3/166 • Number of events 3 • From first dose date up to 21 days after last dose (up to 55 weeks)	4.2% 7/167 • Number of events 7 • From first dose date up to 21 days after last dose (up to 55 weeks)	5.3% 4/76 • Number of events 4 • From first dose date up to 21 days after last dose (up to 55 weeks)	0.00% 0/75 • From first dose date up to 21 days after last dose (up to 55 weeks)

Additional Information

Clinical Trial Disclosure

Astellas Pharma Global Development, Inc

Phone: 800-888-7704

Email: astellas.resultsdisclosure@astellas.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
• Publication restrictions are in place

Restriction type: OTHER